Division of Nephrology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Ratchathewi, 10400 Bangkok, Thailand.
Front Biosci (Landmark Ed). 2023 Aug 15;28(8):167. doi: 10.31083/j.fbl2808167.
Parathyroid hormone (PTH) is an endocrine peptide found exclusively in the parathyroid glands, whereas parathyroid hormone-related protein (PTHrP) is expressed in a wide range of tissues and organs and exerts endocrine, paracrine, and autocrine actions. PTH and PTHrP have a similar homology, sharing the initial 13 amino acid residues at the N-terminus and binding to the same type 1 PTH receptor (PTH1R), which regulates calcium homeostasis. An abnormal increase in PTH production can occur in primary and secondary hyperparathyroidism, whereas PTHrP can be produced in large quantities by malignant cancer cells from solid organs. In addition to increased bone resorption and hypercalcemia, recent evidence suggests that excess PTH and PTHrP can result in protein-energy wasting, malnutrition, and cachexia. Through binding to PTH1R and activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase A in white adipose tissue, PTH and PTHrP can stimulate the expression of thermogenic genes causing adipose tissue browning. This change results in an increase in resting energy expenditure, loss of muscle and fat mass, and weight loss. These findings provide a mechanistic link for the long-established relationship between hyperparathyroidism and myopathy, as well as cancer and cachexia. The purpose of this review is to provide a summary of the emerging evidence from both experimental and clinical studies on the role of PTH and PTHrP in protein-energy malnutrition.
甲状旁腺激素（PTH）是一种仅存在于甲状旁腺中的内分泌肽，而甲状旁腺激素相关蛋白（PTHrP）则在广泛的组织和器官中表达，并发挥内分泌、旁分泌和自分泌作用。PTH 和 PTHrP 具有相似的同源性，在 N 端共享最初的 13 个氨基酸残基，并与相同的 1 型 PTH 受体（PTH1R）结合，该受体调节钙稳态。原发性和继发性甲状旁腺功能亢进症可导致 PTH 产生异常增加，而实体器官的恶性癌细胞可大量产生 PTHrP。除了增加骨吸收和高钙血症外，最近的证据表明，过量的 PTH 和 PTHrP 可导致蛋白质-能量消耗、营养不良和恶病质。通过与 PTH1R 结合并激活白色脂肪组织中的环腺苷酸单磷酸（cAMP）依赖性蛋白激酶 A，PTH 和 PTHrP 可刺激引起脂肪组织褐变的产热基因的表达。这种变化导致静息能量消耗增加、肌肉和脂肪量减少以及体重减轻。这些发现为长期确立的甲状旁腺功能亢进与肌肉病以及癌症与恶病质之间的关系提供了一种机制联系。本综述的目的是总结实验和临床研究中关于 PTH 和 PTHrP 在蛋白质-能量营养不良中的作用的新证据。
